Last year we reported the results of immunochemical studies which demonstrated unequivocally that the synergistic effect of NADH on NADPH-dependent metabolism of various compounds by cytochrome P-450 enzymes in liver microsomes is mediated by cytochrome b5. In addition, we also demonstrated that cytochrome b5 also plays a role in the NADPH-dependent metabolism of various compounds even in the absence of NADH. However, the anti-cytochrome b5 antibody inhibited drug metabolism more than it inhibited NADPH oxidation. The objective of this project was therefore to determine the reason for this discrepancy.